This study is part of a national undertaking to demonstrate the effectiveness of two well-defined, short-term psychotherapies as compared with an established anti-depressant medication. Psychotherapists (Ph.D's. and M.D's.) have received specialty training in either cognitive/behavior therapy (C/B) at the University of Pennsylvania or interpersonal psychotherapy (IPT) at Yale University, while psychiatrists have received instruction in administering imipramine and placebo medications in a double-blind design at the Rush Presbyterian St. Luke's Medical Center in Chicago. Patients are undergoing extensive psychological assessments, as well as medical evaluations. Ss are assigned randomly to the several treatment conditions after meeting the stringent "Research Diagnostic Criteria (RDC)" for Major Depressive Disorder (MDD). The major aims of the training and feasibility phase (first 2 years) were to test: 1) the feasibility of applying stringent diagnostic criteria in the selection of patients, 2) the feasibility of experienced clinicians acquiring specific skills in specialty treatments from intensive training and weekly case consultation from the training centers, 3) the capacity of research staff to obtain multiple measurements from patients, therapists, and significant others, and 4) the feasibility of obtaining follow-up assessments of patients post-treatment. Given that these feasibility issues were answered in the affirmative, the pilot treatment outcome study was begun toward the end of Year 2. Ss are being and will be randomly assigned to the treatment conditions, during Years 3 and 4, for a total of 80 Ss treated at each of three collaborative research sites. There will be 6-, 12-, and 18-month follow-up evaluations to assess the prophylactic value of the different treatments in respect to relapse rates and to evaluate the differential effectiveness of the various treatments as revealed by the multiple dependent measures. Years 5 and 6 will consist of completing the collection of follow-up data, analyses of all data, and the write-up of results.